rs191180422

Variant names:

• chr10-1363207-C-A
• rs191180422
• NM_018702.4:c.898G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-1363207-C-A
• chr10-1363207-C-G
• chr10-1363207-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018702.4(ADARB2):​c.898G>T​(p.Glu300*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000757 in 1,321,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: ADARB2 NM_018702.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.18
• Publications: 0 publications found

Genes affected

ADARB2 (HGNC:227): (adenosine deaminase RNA specific B2 (inactive)) This gene encodes a member of the double-stranded RNA adenosine deaminase family of RNA-editing enzymes and may play a regulatory role in RNA editing. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADARB2	NM_018702.4	c.898G>T	p.Glu300*	stop_gained	Exon 3 of 10	ENST00000381312.6	NP_061172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADARB2	ENST00000381312.6	c.898G>T	p.Glu300*	stop_gained	Exon 3 of 10	1	NM_018702.4	ENSP00000370713.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.57e-7 AC: 1 AN: 1321444 Hom.: 0 Cov.: 32 AF XY: 0.00000153 AC XY: 1 AN XY: 654280

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27028

American (AMR) AF: 0.00 AC: 0 AN: 30422

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22516

East Asian (EAS) AF: 0.00 AC: 0 AN: 29526

South Asian (SAS) AF: 0.00 AC: 0 AN: 71392

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5418

European-Non Finnish (NFE) AF: 9.55e-7 AC: 1 AN: 1046668

Other (OTH) AF: 0.00 AC: 0 AN: 53914

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.55	D
BayesDel_noAF	Pathogenic	0.55
CADD	Pathogenic	37
DANN	Uncertain	0.99
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.011
FATHMM_MKL	Uncertain	0.80	D
PhyloP100		3.2
Vest4		0.18
GERP RS		3.3
Mutation Taster		=18/182	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs191180422; hg19: chr10-1405402;